Travelers' Diarrhea

Earl H. Eye, Jr., M.D.
Earl H. Eye, Jr., M.D. is an Infectious Disease Specialist and Pulmonologist
with the Clinic for Pulmonary and Infectious Diseases.

International travel affects the lives of 100 million people each year. Diarrhea will occur in 30-50% of the thirty million U.S. travelers who spend three or more weeks traveling in the developing countries of the world.¹ Symptoms usually begin within two week of arrival in the country, with a typical incubation period from exposure of 3-5 days.² In most cases symptoms are mild, short-lived, and resolve in 1-5 days. Rare cases are severe enough to warrant hospitalization. In at least 80% of cases the cause is an infectious agent (Table 1). The most common causes are gram negative bacteria, but viruses and intestinal parasites may also occur.

Epidemiology

The risk of infection and types of organism involved varies by country and time of year.³ The following are the most common causes:

Bacterial: Enterotoxigenic, Enteroaggressive, Enteropathogenic, and Enterohemorrhagic (current Japan epidemic) E. coli (40%) occurs in almost every country, and are most common during the summer months. Shigella and Enteroinvasive E. coli (10%) typically produce more symptoms and may have fever and bloody diarrhea in a world wide, summer distribution. Aeromonas — worldwide, summer — and Plesiomonas — worldwide, summer, fish source — together account for 5%. Campylobacter jejuni (3%) — worldwide, year round, especially winter — and other less common organisms (i.e. Vibrio cholera — water related, Indian subcontinent and South American, currently epidemic; Vibrio parahemolyticus — coastal areas, summer, immunosuppressed especially alcoholics; Yersinia sp. — water, year round, worldwide) should be considered in studies exclude more common causes.^4,5 Staph aureus, Bacillus cerus, and Clostridia welchii exotoxin food poisoning also occur.

Virus: Rotavirus, enteric adenovirus, Astrovirus, Calicivisus and Norwalk agent (10%) — young people, worldwide, group related (boats, tour bus, etc.), winter predominance —usually produce milder, self-limited infections.

Protozoa: (5%) Giardia lamblia — mountainous areas, water, especially Russia; Entoamoeba histolytica — poor hygiene areas, summer; Cryptosporidium parvum — waterborne, especially Russia and South America; Isospora belli — fecal-oral, tropic; Enterocytozoon bieeusi — usually in AIDS; Nosema conori — usually AIDS; Cyclospora cayetanensis — Asia, higher frequency in immunocompromised patients. Malaria can have diarrhea as an early manifestation. (See Table 1 on next page.)

Presentation

Travelers' diarrhea is considered a syndrome because of the number of etiological organisms.¹ It is defined as the passage of 3 or more loose stools in a 24 hour period with at least one symptom such as nausea, vomiting, cramps, fever, fecal urgency, tenesmus, or passage of blood, mucoid stools. For practical purposes one or two loose stools with symptoms will prompt most travelers to begin treatment before they develop the full syndrome. Most travelers will experience four or five loose stools per day. When untreated diarrhea will last 4-5 days in 85%. Up to 10% of cases will last longer than one week, and 1-2% will have persistent symptoms beyond one month. Diarrhea is accompanied by abdominal cramps in 50-73%, malaise in 50-58%, nausea in 46-50%, feverish feeling in 37%, bloody dysentery in 2-10%, and vomiting in 8-15%. More than half of the cases are mild and do not confine the travelers' activities, but 20% are severe and will confine the traveler to the hotel room for 2-3 days.⁷ More than one attack can be experienced on the same trip. (Table 2)

Host Factors

Risk factors for disease include age, with young children and elderly travelers more commonly and severely infected. Young adults under 30 years of age have higher rates of diarrhea. Those who live in the non-commercialized regions, especially with indigenous tribes and in the rainforest will have high rates of diarrhea. Duration of time in the country increases risk. Ingestion of local water supplies, non-sealed bottled water, swimming, or using ice — even with alcoholic drinks — increases risk. Food is the major source of transmission in all studies. Street vendors, uncooked food of any type — especially meats and shellfish, salads, unpasturized milk, cheese, and ice cream — increase risk and should especially be avoided by pregnant females due to the risk of brucellosis. Excessive fatigue, stress, and consumption of alcohol further increased risk in several studies.⁸

Diagnosis

Typically diagnosis will not occur since the traveler will institute treatment on symptomatic grounds. Should a patient have or develop symptoms on return from a trip, recommended evaluation would include stool culture and smears for ova and parasites, with stool smears for the presence of pus and blood. For the 1-2% of cases that persist with diarrhea for more than two weeks, additional work up should include endoscopy to exclude other causes, and for biopsy of small intestines to exclude Giardia, Microsporidosis, and Cyclospora.⁹ Barium studies should not be performed until studies have been ordered for pathogens. Occasionally, special studies will be needed including special cultures for Yersinia, Vibrio, Aeromonas, Plesimonas, or identification of toxigenic E. coli strains. Serology for amebae and stool stains may be helpful.

Treatment

Most cases of diarrhea require only symptomatic therapy. (Table 3) Treatment measures are broken down into the following components:

Hydration: to avoid the adverse consequences of volume loss and to improve overall sense of well being.

Secretory: diarrhea control with symptomatic treatment of abdominal cramps and pain.

Organism eradication: with the development of fever, severe systemic symptoms, or cramping and bloody diarrhea and antibiotic may be indicated. In the past, doxycycline and sulfa have been effective. With the overuse in the developing countries, most organisms are now resistant. The quinolones (Ciprofloxin) have now become the treatment of choice for most infections, including Salmonella (markedly lessens the incidence of post antibiotic carriage) and Shigella. There are still a few areas where trimthoprim / sulfamethoxazole can be used, including Central Mexico, and for Isospora and Cyclospora. Furazolidone may be used for pregnant women and children for whom quinolones are contraindicated. Astreonam (Azactam®) given orally has been effective in experimental studies. Oral third generation cephalosporins (Vantin®, Suprex®) may be considered. In addition, other drugs not available in the U.S. have been used. Anti-diarrheal medications can be purchased in foreign countries, but their use should be discouraged since many contain chloramphenicol or other components which can cause neurotoxicity.¹⁰

Prevention

Standard dogma has taught that the traveler should avoid drinking local water supplies, eating uncooked or peeled fruits, raw meats, unpasturized milk and cheese, and salads. Prior studies looked at the incidence of diarrhea in those who followed precautions versus those less cautious. The incidence of diarrhea illness was unchanged.^10,11 Despite this finding, most travelers are given the following recommendations:

Drink carbonated water (pH kills coliforms in dose dependent fashion): Bottled water and unbottled water frequently have high coliforms counts. For regular, clear water, boil for 3-5 minutes or place 2 drops of 5% bleach in one quart for 30 minutes, or use 2% tincture of iodine — available as Globuline®, Portable-Aqua®, and Coughlan's® from sporting good stores.

Pepto-Bismol®: at a dose of 2.1 gms/day reduced the incidence of diarrhea from 51% to 14%. It can be used in children above age 3. Probiotics — such as lactobacilli or Saccaromyces boulardii — look promising for prevention of diarrhea.¹⁰

Antibiotics: indicated for those whose trip is so important that no interruption can be tolerated (i.e. diplomats, business traveler, performing artists, and those with medical predisposition — immunosuppressed, gastrectomy, achlorhdria, taking H2 or proton pump inhibitors, severe liver disease, chronic severe systemic disease, inflammatory bowel disease or short bowel syndrome, or diabetes mellitus). Various antibiotics and dosage regiments have been used for prevention. Unless you know that the common bacteria are susceptible to other agents [doxycycline (Vibramycin®), sulfamethoxazole/trimethaprim (Septra®), or trimethaprim (Polytrim®)], fluroquinolones are the best drugs.¹² These include ciprofloxin 500 mg daily, ofloxin 400 mg daily, or norfloxin 400 mg daily PO. Remember that young children cannot take these drugs due to joint injury potential. For children under 16 and pregnant females, furazolidone 8 mg/kg/day in 4 divided doses for 5 days, or SMX/TMX, erythromycin, or aztreonam 150 mg PO tid may be used. Newer oral third and fourth generation cephalosporins may be considered. All antibiotics can have adverse effects including allergic reactions (all), tendon and join damage (fluroquinolones), Stevens-Johnsons syndrome (SMX/TMS), overgrowth of C. difficele and photosensitivity (doxycycline), and candida vaginitis (all). Overgrowth of other pathogenic organisms can occur. Newer antibiotics are under evaluation including Bicozamycin®, and Azactam®.¹⁰

Vaccines: Hepatitis A vaccine is available as HAVRIX® or VAQTA®. Hepatitis B is now routine for all children, and should be recommended to adults for high endemic areas. Polio vaccine should be up to day. Oral typhoid vaccine is available and a new, one injection, typhoid vaccine (VICPS®) can be used. Vibro oral vaccine (not effective against the new 01399HL) prevents the effects of the enterotoxin, and is thought to be cross protective with Enterotoxigenic E. coli. Vaccines for Norwark and Rotavirus are under development. Current recommendations are available from the CDC [phone (404)332-4559; fax (404)332-4565]. Patient handouts for traveling instructions are also available from this source. Internet users can reach the CDC at <http://www.cdc.gov> with information about publications, products, and access to the Morbidity and Mortality Weekly Report.¹²

Persistent Chronic Diarrhea

Diarrhea that persists greater than two weeks will occur in 1-2% of travelers. This can be due to a variety of causes. Giardia may not even present for weeks after a trip, and Cryptosporidosis, cyclospora, and amebias must be considered. Persistent bacterial infections must be excluded. The development of a post-dysenteric syndrome similar to irritable bowel syndrome may occur, which may be made worse by the tendency to increase fluid intake, many of which contain carbohydrates, with the persistent diarrhea. The unmasking of pre-existing inflammatory bowel disease is well described. Tropical spure occurs after diarrhea infection. The work-up should include three bowel specimens for culture for Salmonella, Shigella, Yersinia, Campylobacter, Aermonas, Plesimonas, and special request for enteroinvasive E. coli. Three other specimens should be sent for pus, blood, and O&P. Clostridia difficle toxin assay should be requested. If blood is found in the stool on rectal exam, then flexible sigmoidoscopy with either barium enema or colonoscopy should be performed. If these studies are not helpful, or if history suggests a malapsorption syndrome, then serum studies for malabsorption (including serum carotine, B12, folate, and prothombin time) should be done. Finally, an upper endoscopy with aspirates of duodenum secretions and biopsy should be performed for spure, parasites, and quantitative bacterial culture to exclude bacterial overgrowth. If all studies are negative, than patients are classified as having postdysenteric irritable bowel syndrome, and treated with dietary fiber, and occasionally antispasmodic agents.⁷

REFERENCES

1. Symposium: Travelers' Diarrhea, 35th ICAAC, 1996.
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3. DuPont HL. Travelers' diarrhea. Which antimicrobial? Practical Therapy. 1993; 45(6):910-917.
4. Farthing MJ. Travelers' diarrhea. Gut. 1994; 35:1-4.
5. Lochie C. A new look at travelers' diarrhea (Symposium). The Practitioner. 1994; 238:624-628.
6. Ball JM, et al. Age dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science. 1996; 272:101-104.
7. Chak A, et al. Travelers' diarrhea. Gastroenterology Clin N A. 1993; 22(3):549-561.
8. Okhuysen PC. Travelers' diarrhea. Prevention and Treatment. 1992; 76(6):1357-1373.
9. Cascon J, et al. Cyclospora in patients with travelers's diarrhea. 1995; 27(5):511-514.
10. Scarpignato C, Rampal P. Prevention and treatment of travelers' diarrhea: a clinical pharmacological approach. 1995; 41(suppl. 1):48-81.
11. Loewenstein MS, et al. Tourista at an international congress in Mexico. Lancet. 1993; 1:529-531.
12. Morbidity and Mortality Weekly Report. 1995; 44(22):429-431.